Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis
Integrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progr...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/8/1360 |
| _version_ | 1797436335241297920 |
|---|---|
| author | Siamak A. Kamranvar Deepesh Kumar Gupta Anishia Wasberg Liangwen Liu Joan Roig Staffan Johansson |
| author_facet | Siamak A. Kamranvar Deepesh Kumar Gupta Anishia Wasberg Liangwen Liu Joan Roig Staffan Johansson |
| author_sort | Siamak A. Kamranvar |
| collection | DOAJ |
| description | Integrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progression through the G2 and M phases was monitored by live-cell imaging and immunofluorescence staining in adherent and non-adherent fibroblast cells. Non-adherent cells, as well as adherent cells lacking FAK activity due to suppressed expression or pharmacological inhibition, exhibited a prolonged G2 phase and severely defect centrosome separation, resulting in delayed progress through the early mitotic stages. The activation of the critical mitotic regulator PLK1 and its indirect target Eg5, a kinesin-family motor protein driving the centrosome separation, were reduced in the cells lacking FAK activity. Furthermore, the absence of integrin adhesion or FAK activity destabilized the structural integrity of centrosomes and often caused detachment of pericentriolar material from the centrioles. These data identify a novel adhesion-dependent mechanism by which integrins via FAK and PLK1 contribute to the regulation of the cell cycle in the G2 and early M phases, and to the maintenance of genome integrity. |
| first_indexed | 2024-03-09T11:01:08Z |
| format | Article |
| id | doaj.art-633b16fa03534e1cadbceb6aa35d1160 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:01:08Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-633b16fa03534e1cadbceb6aa35d11602023-12-01T01:15:25ZengMDPI AGCells2073-44092022-04-01118136010.3390/cells11081360Integrin-Mediated Adhesion Promotes Centrosome Separation in Early MitosisSiamak A. Kamranvar0Deepesh Kumar Gupta1Anishia Wasberg2Liangwen Liu3Joan Roig4Staffan Johansson5Department of Medical Biochemistry and Microbiology (IMBIM), Biomedical Center, Uppsala University, 75123 Uppsala, SwedenDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Medical Biochemistry and Microbiology (IMBIM), Biomedical Center, Uppsala University, 75123 Uppsala, SwedenDepartment of Medical Cell Biology (MCB), Biomedical Center, Uppsala University, 75123 Uppsala, SwedenCell Signaling Group, Molecular Biology Institute of Barcelona (IBMB-CSIC), 08028 Barcelona, SpainDepartment of Medical Biochemistry and Microbiology (IMBIM), Biomedical Center, Uppsala University, 75123 Uppsala, SwedenIntegrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progression through the G2 and M phases was monitored by live-cell imaging and immunofluorescence staining in adherent and non-adherent fibroblast cells. Non-adherent cells, as well as adherent cells lacking FAK activity due to suppressed expression or pharmacological inhibition, exhibited a prolonged G2 phase and severely defect centrosome separation, resulting in delayed progress through the early mitotic stages. The activation of the critical mitotic regulator PLK1 and its indirect target Eg5, a kinesin-family motor protein driving the centrosome separation, were reduced in the cells lacking FAK activity. Furthermore, the absence of integrin adhesion or FAK activity destabilized the structural integrity of centrosomes and often caused detachment of pericentriolar material from the centrioles. These data identify a novel adhesion-dependent mechanism by which integrins via FAK and PLK1 contribute to the regulation of the cell cycle in the G2 and early M phases, and to the maintenance of genome integrity.https://www.mdpi.com/2073-4409/11/8/1360integrinFAKPLK1centrosomemitosisEg5 |
| spellingShingle | Siamak A. Kamranvar Deepesh Kumar Gupta Anishia Wasberg Liangwen Liu Joan Roig Staffan Johansson Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis Cells integrin FAK PLK1 centrosome mitosis Eg5 |
| title | Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis |
| title_full | Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis |
| title_fullStr | Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis |
| title_full_unstemmed | Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis |
| title_short | Integrin-Mediated Adhesion Promotes Centrosome Separation in Early Mitosis |
| title_sort | integrin mediated adhesion promotes centrosome separation in early mitosis |
| topic | integrin FAK PLK1 centrosome mitosis Eg5 |
| url | https://www.mdpi.com/2073-4409/11/8/1360 |
| work_keys_str_mv | AT siamakakamranvar integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis AT deepeshkumargupta integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis AT anishiawasberg integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis AT liangwenliu integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis AT joanroig integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis AT staffanjohansson integrinmediatedadhesionpromotescentrosomeseparationinearlymitosis |